Evolution of safety profile of different therapeutic alternatives in Restless Legs Syndrome (RLS)

Abstract

Introduction To compare safety and tolerability of different therapeutic strategies in the management of Restless Legs Syndrome (RLS) in our Neurophysiology Unit, as well as their evolution over time. Materials and Methods Retrospective analysis of the safety profile of the different therapies used on every patient in our clinic suffering RLS +/- Periodic Limb Movement (PLM) from year 2000 until 2012. Results A total of 138 subjects visited our clinic complaining about PLM (92%), RLS (70.3%) or PLM + RLS (62.3%), with an average age of onset of 55.5 years, 50% women. 18.8% of patients did not require any treatment. Of the other subjects (n=112), 50.7% (n=70) were treated in some moment of their disease with clonazepam (CLZ), 41.3% (n=57) with ropinirole (RPX), and 37.7% (n=52) with rotigotine (RTG). Considering the different availability of these drugs over time, the medication more frequently administered was CLZ, followed by RPX and RTG. Despite this, the average length of treatment with CLZ (2.5 years) was statistically higher to that of RPX (2 years) and RTG (1.4 years) (p=0.005, Kruskal- Wallis test), while not showing this significant difference between RPX and RTG. 12.9% of CLZ treated patients showed some adverse event (AE) during treatment, this number increasing to a 15.8% in the RPX group, while only happening in 5.8% of the RTG patients. The most frequent AEs with CLZ were dizziness and somnolence; unspecified malaise and somnolence in the RPX group, and site application reactions in the case of RTG. Among the AEs causing drug withdrawal or switching, we must highlight the augmentation phenomenon, which was shown in 37.1% of patients treated with CLZ, 40.4% of the RPX group, and 0% in the RTG group (p 0.0001, Chi square test). Other AEs causing treatment withdrawal were: lack of efficacy (24.3% in the CLZ group, 42.1% in the RPX patients, 5.8% with RTG), and adherence to the treatment (1.4% of subjects with CLZ, 1.8% with RPX and 0% with RTG). Conclusion New therapeutic strategies in the management of RLS ensure not only efficacy, but also a safe and very well tolerated control of the patient, especially with long term treatments (augmentation phenomena).